AbbVie Announces Positive Top-Line Results From Second Phase 3 Study Investigating Elagolix in Patients with Endometriosis
- Study meets co-primary efficacy endpoints and full results will be presented at a medical conference in 2016
- Results show Elagolix reduces endometriosis-associated pain (menstrual and non-menstrual pelvic pain) compared to placebo
- New Drug Application for endometriosis anticipated in 2017
NORTH CHICAGO, Ill., Feb. 10, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), in cooperation with Neurocrine Biosciences, Inc. (NASDAQ: NBIX), announced positive top-line results from the second of two replicate pivotal Phase 3 clinical trials evaluating the efficacy and safety of Elagolix in premenopausal women who suffer pain from endometriosis. Trial results show that after six months of continuous treatment, both doses of Elagolix (150 mg once daily and 200 mg twice daily) met the study's co-primary endpoints. Elagolix reduced scores of menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis, at month three and month six, as measured by the Daily Assessment of Endometriosis Pain scale. Responder rates for the co-primary endpoints from this second Phase 3 pivotal study are consistent with results from the first Phase 3 pivotal study.
Table 1. Proportion of Responders for Co-Primary Endpoints
PROPORTION OF RESPONDERS AT MONTH 3 & MONTH 6* – n (%)
Non-Menstrual Pelvic Pain
(N = 353, 355)
Elagolix 150 QD**
(N = 221)
Elagolix 200 BID***
(N = 225)
p-values vs. placebo
p-values vs. placebo
*LOCF analysis also accounts for rescue analgesic use
** QD = once daily
*** BID = twice daily
"Endometriosis affects an estimated 176 million women worldwide.1 Patients voice their frustration about the need for more treatment options to medically manage endometriosis and its often debilitating pain," said Michael Severino, M.D. executive vice president, research and development, and chief scientific officer, AbbVie. "In an effort to address this need, AbbVie conducted the largest clinical trials in endometriosis to date. We are pleased with the outcomes of the Pivotal trials thus far. AbbVie will continue to pursue Elagolix as a potential new treatment for the disease's most common symptoms, including pain related to menstruation and chronic pelvic pain throughout the menstrual cycle."2
The safety profile of Elagolix in this study was consistent with observations from the first Phase 3 pivotal study and prior Elagolix studies. Among the most common treatment-emergent adverse events (TEAEs) were hot flush, headache, and nausea. As anticipated by the mechanism of action, some AEs, such as hot flush, other hypoestrogenic TEAEs and changes in bone mineral density (BMD) were dose-dependent. Overall discontinuation rates were similar across treatment groups (25.3%, 21.2%, and 19.7% for placebo, 150 mg once daily and 200 mg twice daily, respectively); discontinuations specifically due to TEAEs were 6.1%, 4.4%, and 10.0% for placebo, 150 mg once daily and 200 mg twice daily, respectively. The mean percent change from baseline in BMD at the lumbar spine (LS) at month six is provided in Table 2 below. The BMD finding for Elagolix 150 mg QD is consistent with observations from prior Phase 2 studies and as expected, a dose-dependent effect is seen for Elagolix 200 mg BID.
Table 2. Mean Percent Change from Baseline in Bone Mineral Density at Lumbar Spine (Month 6)
Mean % Change from Baseline at Lumbar Spine (Month 6)
Placebo (n = 269)
Elagolix 150 QD (n = 174)
Elagolix 200 BID (n = 180)
Between Group Comparison vs. Placebo at Month 6
P value vs. PBO (<0.001 for both doses)
The top-line results are from a six-month, group-level analysis. Patients in the trial will continue on in either post-treatment follow-up or a blinded extension study for an additional six-month safety and efficacy evaluation. AbbVie intends to present detailed results from its two Phase 3 trials at a future medical conference in 2016. AbbVie will complete the clinical database in anticipation of a New Drug Application submission for endometriosis in 2017.
The first Phase 3 trial (M12-665) was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Elagolix in 872 women, age 18 to 49, with moderate-to-severe endometriosis-associated pain. It was conducted at approximately 160 sites in the United States, Puerto Rico and Canada.
This second Phase 3 trial (M12-671) employed the same design as the first Phase 3 pivotal trial but was multinational and included 815 women with moderate-to-severe endometriosis-associated pain across 226 sites in 13 countries (US and 12 Ex-US countries). There was equal representation of enrollment from US and Ex-US countries. Together, these two Phase 3 pivotal studies evaluated the safety and efficacy of Elagolix in nearly 1700 women with moderate-to-severe endometriosis associated pain, representing the largest prospective randomized endometriosis trials conducted to date.
Endometriosis occurs when the cells that normally line the uterus begin to grow outside of the uterus.2 These growths are called lesions and can occur on the ovaries, the fallopian tubes, or other areas near the uterus.3,4 There is no cure for endometriosis, which is currently managed with oral contraceptives, NSAIDs, opioids, and GnRH agonists. When these medical treatments fail, surgical interventions (e.g., laparotomy or laparoscopy) are often pursued, and again, are not curative.2 Endometriosis can also be associated with infertility.2
Elagolix is an orally administered gonadotropin-releasing hormone (GnRH) antagonist that is currently being investigated in diseases that are mediated by sex hormones, such as uterine fibroids and endometriosis. To date, Elagolix has been studied in over 40 clinical trials totaling more than 3,000 subjects. Phase 3 trials of Elagolix for the management of uterine fibroids are also ongoing.
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 The World Endometriosis Research Foundation: Facts about Endometriosis. http://endometriosisfoundation.org/Facts-about-endometriosis.pdf. Accessed February 1, 2016.
2 Mayo Clinic. Diseases and Symptoms: Endometriosis Fact Sheet. http://www.mayoclinic.org/diseases-conditions/endometriosis/basics/symptoms/con-20013968. Accessed February 1, 2016.
3 MM, Silverberg K, Olive DL. Endometriosis and Adenomyosis. IN: Copeland LJ, Jarrell JF, eds. Textbook of Gynecology. 2nd ed. Philadelphia, PA: WB Saunders; 2000:687-722.
4 The American College of Obstetricians and Gynecologists. ACOG Education Pamphlet AP013: Endometriosis. Washington, DC: September 2008. ISSN 1074-8601.